Table 2 Potential pre-analytical variables*

Collection technique

• Hypodermic needle gauge and speed of draw.

• In-dwelling catheter—washouts are important!

• Order of draw with multiple tubes—anticoagulant contamination.

• Stasis (tourniquet).

• Sampling during infusion—time and site.

• Blood volume per tube—variation of additive concentration.

• Mixing technique—no shaking, use inversion.

• Positional effect—supine vs. erect.

Timing and physiological at sample collection

• Time of day of collection (circadian rhythm), urine—first void vs. midstream, random vs. 12/24h

• Hydration status

• Fasting or non-fasting status—lipemia

• Menstruation

• Stress (needle phobia, etc.—limited control possible)

• Time point relevant to expected change—e.g., lag times for pharmacodynamic effects

Sample processing

• Matrix selection (collection tube type) (Dakappagari et al. 2017)

• Sample identification

• Centralized processing vs. processing at clinical site

• Time between collection, processing, and storage

• Mode of transport/storage—time and temperature

• Centrifugation—temperature, speed, and time

• Evaporation, oxidation, and desiccation

• Sunlight, artificial light, and humidity

• Hemolysis

Personal

• Age

• Gender

• Race

• Body mass index

• Diet

• Exercise

• Smoking

• Alcohol

• Caffeine

Physiological

• Pregnancy

• Lactation

• High concentrations of various circulating proteins

• Circulating antibodies (rheumatoid factor, human anti-mouse antibodies, etc.)

• Stress—clinical hypertension

Environmental

• Altitude

• Temperature

• Geographical location

• Seasonal influences

Drugs

• Existing therapies

• Co-medications

• Trial drug